The 6-fluoro-7-substituted quinolonecarboxylic acid derivative represented by the general formula (4) is a compound useful as a raw material of a medicine to be used as an anti-fungus agent and its synthesis intermediate.
Generally, as a method of producing said compound can be mentioned a method comprising introducing a specific substituent to the desired position of a benzene ring first and then forming a quinolone skeleton, and a method comprising introducing a substituent to be a specific precursor to a desired position first, forming a quinolone ring and then converting the substituent to be a precursor to a specific substituent.
In the case of the former, it lacks selectivity to introduce a specific substituent to a desired position and hence it has too many problems to be industrially useful. In the case of the latter, since the selectivity of a position and the reactivity in substitution increase due to the ring closure of a quinolone ring, it is relatively easy to introduce a specific substituent to a desired position.
In the following condensation reaction from the general formula (1) to the general formula (4), there have been difficulties for industrial production regarding the 7-alkylamination of introducing a specific substituent as below. ##STR5##
wherein R.sub.1 represents a lower alkyl group or a cyclo lower alkyl group; R.sub.2 represents a hydrogen atom, a halogen atom or a lower alkoxy group; R.sub.3 represents an optional, functional residue capable of participating in a nucleophilic substitution; X represents --CH.sub.2 --, --NR.sub.4 -- or --O--; R.sub.4 represents a hydrogen atom or a lower alkyl group; Y represents a hydrogen atom, an amino group or a lower alkylamino group bonded to an optional carbon atom on a saturated heterocycle, or a group capable of easily being converted to an amino group or a lower alkylamino group according to a chemical means; and n represents 0 or 1.
Conventionally, the present reaction has obtained an objective compound by heating a compound represented by the general formula (1) and a compound represented by the general formula (2) in a solution (Japanese Patent Public Disclosure No. 252772/1987 and No. 16746/1989), or by converting a 3-position carboxyl group in the general formula (1) to borohydrofluoric acid ester with a view to making the nucleophilic substitution of the 7-position easy, then adding a compound represented by the general formula (2) and heating the reaction mixture in a solution (Japanese Patent Public Disclosure No. 316757/1988).